巨噬细胞通过测量“吃我”信号免疫球蛋白 G (IgG) 来识别吞噬作用的目标。我们测试了之前接触 IgG 是否会影响巨噬细胞的食欲。 IgG 被 Fc 受体识别。为了暂时控制 Fc 受体激活，我们设计了一种 Fc 受体，该受体通过光诱导的 Cry2 寡聚化来激活，从而触发吞噬作用。使用该工具，我们证明阈下 Fc 受体激活会促使小鼠骨髓来源的巨噬细胞在未来的遭遇中对 IgG 更加敏感。先前经历过阈下 Fc 受体激活的巨噬细胞会吞噬更多 IgG 结合的人类癌细胞。吞噬作用的增加是通过两种不同的机制发生的——短期启动和长期启动。长期启动需要新的蛋白质合成和 Erk 活性。短期启动不需要新的蛋白质合成，并且与 Fc 受体迁移率的增加相关。我们的工作表明，IgG 会启动巨噬细胞以增加吞噬作用，这表明治疗性抗体在初始启动剂量后可能会变得更有效。版权所有 © 2024 作者。由爱思唯尔公司出版。保留所有权利。

Macrophages measure the "eat-me" signal immunoglobulin G (IgG) to identify targets for phagocytosis. We tested whether prior encounters with IgG influence macrophage appetite. IgG is recognized by the Fc receptor. To temporally control Fc receptor activation, we engineered an Fc receptor that is activated by the light-induced oligomerization of Cry2, triggering phagocytosis. Using this tool, we demonstrate that subthreshold Fc receptor activation primes mouse bone-marrow-derived macrophages to be more sensitive to IgG in future encounters. Macrophages that have previously experienced subthreshold Fc receptor activation eat more IgG-bound human cancer cells. Increased phagocytosis occurs by two discrete mechanisms-a short- and long-term priming. Long-term priming requires new protein synthesis and Erk activity. Short-term priming does not require new protein synthesis and correlates with an increase in Fc receptor mobility. Our work demonstrates that IgG primes macrophages for increased phagocytosis, suggesting that therapeutic antibodies may become more effective after initial priming doses.Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.